Chemo-Diversification of Plant Extracts Using a Generic Bromination Reaction and Monitoring by Metabolite Profiling

ACS Comb Sci. 2019 Mar 11;21(3):171-182. doi: 10.1021/acscombsci.8b00132. Epub 2019 Jan 17.


A generic procedure for direct bromination of polyphenol in crude plant extracts was developed to generate multiple "unnatural" halogenated natural products for further bioassay evaluation. To better control the halogenation procedure, the bromination was optimized with a flavonoid standard, and the reactions were monitored by high-performance liquid chromatography photometric diode array coupled to the evaporative light scattering detection (ELSD). ELSD detection was successfully used for a relative yield estimation of the compounds obtained. From the halogenation of hesperitin (11), five brominated compounds were obtained. After optimization, the reaction was successfully applied to the methanolic extract of Citrus sinensis peels, a typical waste biomass and also to the methanolic extract of the medicinal plant Curcuma longa. In both cases, the methanolic extracts were profiled by NMR for a rapid estimation of the polyphenol versus primary metabolite content. An enriched secondary metabolites extract was obtained using vacuum liquid chromatography and submitted to bromination. Metabolite profiling performed by ultrahigh purity liquid chromatography time-of-flight high-resolution mass spectrometry revealed the presence of various halogenated products. To isolate these compounds, the reactions were scaled up, and six halogenated analogues were isolated and fully characterized by NMR and high-resolution electrospray ionization mass spectrometry analyses. The antibacterial properties of these compounds were evaluated using in vitro bioassays against multiresistant strains of Staphylococcus aureus and Pseudomonas aeruginosa. Some of the halogenated derivatives obtained presented moderate antibacterial properties.

Keywords: MRSA; antibacterial properties; bioassay; bromination; diversification; metabolite profiling; plant extracts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Citrus sinensis / chemistry*
  • Curcuma / chemistry*
  • Drug Evaluation, Preclinical / methods
  • Halogenation
  • Humans
  • Methanol / chemistry
  • Molecular Structure
  • Plant Extracts / chemistry*
  • Polyphenols / chemistry*
  • Pseudomonas aeruginosa / drug effects
  • Spectrometry, Mass, Electrospray Ionization
  • Staphylococcus aureus / drug effects


  • Anti-Bacterial Agents
  • Plant Extracts
  • Polyphenols
  • Methanol